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Crystal structure of IdnL1Crystal structure of IdnL1
Structural highlights
FunctionPublication Abstract from PubMedMacrolactam antibiotics such as incednine and cremimycin possess an aliphatic beta-amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand-alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic beta-amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3-aminobutanoic acid and 3-aminononanoic acid, respectively. We solved the X-ray crystal structures of IdnL1 and CmiS6 to understand the recognition mechanism of these aliphatic beta-amino acids. These structures revealed that IdnL1 and CmiS6 share a common recognition motif that interacts with the beta-amino group of the substrates. However, the hydrophobic side-chains of the substrates are accommodated differently in the two enzymes. IdnL1 has a bulky Leu220 located close to the terminal methyl group of 3-aminobutanoate of the trapped acyl-adenylate intermediate to construct a shallow substrate-binding pocket. In contrast, CmiS6 possesses Gly220 at the corresponding position to accommodate 3-aminononanoic acid. This structural observation was supported by a mutational study. Thus, the size of amino acid residue at the 220 position is critical for the selection of an aliphatic beta-amino acid substrate in these adenylation enzymes. Proteins 2017; 85:1238-1247. (c) 2017 Wiley Periodicals, Inc. Biochemical characterization and structural insight into aliphatic beta-amino acid adenylation enzymes IdnL1 and CmiS6.,Cieslak J, Miyanaga A, Takaku R, Takaishi M, Amagai K, Kudo F, Eguchi T Proteins. 2017 Jul;85(7):1238-1247. doi: 10.1002/prot.25284. Epub 2017 Mar 29. PMID:28316096[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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